A convenient one-pot synthesis of new 3-(4-aryl-5-oxo-5,6,7,8-tetrahydro- 4H-chromen-2-yl)-2H-chromen-2-ones

Article abstract of DOI:10.1002/jhet.5570440331

(Chemical Equation Presented) Anhydrous zinc bromide catalysed reactions of arylidine-3-acetyl coumarins (1a-c) and 5,6-benzoanalogs of arylidine 3-acetyl coumarins (4a,4b) with 1,3-cyclohexanedione gives 3-(4-aryl-5-oxo-5,6,7,8- tetrahydro-4H-chromen-2yl

Full text of DOI:10.1002/jhet.5570440331

May-Jun 2007
707
A Convenient One-pot Synthesis of New 3-(4-Aryl-5-oxo-5,6,7,8-
tetrahydro-4H-chromen-2-yl)-2H-chromen-2-ones
V. Rajeswar Rao* and V. Ravinder Reddy
Department of Chemistry,
National Institute of Technology,
Warangal – 506 009, A.P., India.
e-mail: vrajesw@yahoo.com; suneela72@yahoo.com
Received March 16, 2005
R
O
2
R
2
O
O
O
O
Anhy. ZnBr
Toluene
2
+
R
5
4
O
R
R
4
5
O
O
R
1
R
R
1
R
3
(2)
(1)
O
R
3
(3)
Anhydrous zinc bromide catalysed reactions of arylidine-3-acetyl coumarins (1a-c) and 5,6-
benzoanalogs of arylidine 3-acetyl coumarins (4a,4b) with 1,3-cyclohexanedione gives 3-(4-aryl-5-oxo-
5,6,7,8-tetrahydro-4H-chromen-2yl)-2H-chromen-2-ones (3a, 3c) and 5,6-benzoanalogs of 3-(4-aryl-5-
oxo-5,6,7,8-tetrahydro-4H-chromen-2yl)-2H-chromen-2-one (5a,5b). Under similar conditions arylidine-3-
acetylcoumarins (1a, 1b,1d, 1e, 1f) and 5,6-benzoanalog of arylidine 3-acetyl coumarin (4b) react with
5,5-dimethyl-1,3-cyclohexanedione (dimedone) yielding 3-(4-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
4H-chromen-2-yl)-2H-chromen-2-ones (3d-3h) and the 5,6-benzoanalog of 3-(4-aryl-7,7-dimethyl-5-oxo-
5,6,7,8-tetrahydro-4H-chromen-2-yl)-2H-chromen-2-one (5c).
J. Heterocyclic Chem., 44, 707 (2007).
this carbonyl carbon will become more positively
charged and is easily attacked by nucleophillic enolic
hydroxy group to give the cyclised compound 3 and 5.
During the above reaction there is no formation of
Micheal adducts between cyclic 1,3-diketones and
chalcones. This is confirmed from analytical and
spectral data.
INTRODUCTION
There is a continuous interest in the synthesis of
benzopyrans, since they possess antijuvenile hormone
activity [1], antianaphylactic activity in trachea [2] and
are found to be antiallergic [3,4], antinflammatory [5],
and anticancer [6] agents and also helpful in diabetic
complications [7]. In continuation of our earlier work [8-
10] on the synthesis of benzopyrans, we report here a new
one step efficient synthesis of 3-(4-aryl-5-oxo-5,6,7,8-
tetrahydro-4H-chromen-2yl)-2H-chromen-2-ones in good
yields (65-78%).
The synthesis utilizes the condensation of cyclohexane-
1,3-dione and 5,5-dimethyl-1,3-cyclohexanedione with
different chalcones (1a-1f) derived from 3-acetyl
coumarins and the corresponding 5,6-benzo derivatives
(4a-c) of 3-acetyl coumarins.
The formation of these compounds (3-5) may be
explained by the initial formation of a 1:1 adduct
which presumably underwent cyclisation in the
presence of ZnBr2 catalyst as shown in Scheme-1.
The Lewis acid, zinc bromide will effectively polarize
the carbon-oxygen double bond by coordinating the
oxygen to the electron deficient Zn in ZnBr2. Due to
The infrared spectra of the newly prepared chromen
derivatives (3-5) are consistent with their structures.
They exhibit strong carbonyl bands at 1717-1741 cm-1
for lactone and 1656-1670 cm-1 for ketone respectively.
The C-O stretching is observed at 1205-1213 cm-1. The
1H nmr spectrum of 3a exhibited besides the usual
signals, two characteristic doublets at ꢀ 4.47 (1H, J = 6
Hz, C4-H) and at ꢀ 6.66 (1H, J = 3 Hz, C3-H). Its mass
1
spectrum gave a peak at m/z 370 (M+). The H nmr
spectrum of 3d showed besides usual signals, the
protons at C6 as an AB quartet at ꢀ 2.14 – 2.33. The
appearance of AB quartet clearly showed that two
methylene protons are non equivalent or not identical.
The aniosotropic effect of the adjacent carbonyl is
responsible for their difference. The protons of C4 and
C5 have appeared as doublets at ꢀ 4.45 (d, 1H, J = 6 Hz,
C4-H) and 6.66 (d, 1H, J = 6 Hz, C5-H).

708
V. R. Rao and V. R. Reddy
Vol 44
Scheme-1
R2
O
R2
O
O
Anhy. ZnBr2
O
O
+
R4
R5
R4
R5
Toluene
O
O
O
R1
O
R1
R3
(1)
H
(2)
O
1a : R1 = R2 = R3 =H
1b : R1 = R2 = H, R3 = F
1c : R1 = R2 = H, R3 = OCH3
2a : R4 = R5 = H
2b : R4 = R5 =CH3
1d : R1 = Br, R2 = H, R3 = OCH3
1e : R1 = Br, R = H, R3 = F
1f : R1 = Cl, R2 = R3 = H
R3
R2
O
O
R2
OH
O
O
O
R4
R5
R1
..
R4
R5
HO
O
..
R1
H
O
O
R3
R3
-H2O
R2
O
O
1
O
8
7
R4
R1
2
R5
6
5
3
4
3a : R1 = R2 = R3 = R4 = R5 = H
3b : R1 = R2 = R4 = R5 = H, R3 = F
O
3c : R1 = R2 = R4 = R5 = H, R3 = OCH3
3d : R1 = R2 = R3 = H, R4 = R5 = CH3
3e : R1 = Br, R2 = H, R3 = OCH3, R4 = R5 = CH3
3f : R1 = R2 = H, R3 = F, R4 = R5 = CH3
3g : R1 = Br, R2 = H, R3 = F, R4 = R5 = CH3
3h : R1 = Cl, R2 = R3 = R4 = R5 = CH3
R3
(3)
O
O
O
O
O
Anhy. ZnBr2
Toluene
1
O
8
+
R4
R5
7
O
R4
R5
2
O
3
6
R3
4
5
O
(2)
(4)
2a : R4 = R5 = H
2b : R4 = R5 = CH3
4a : R3 = H
4b : R3 = F
(5)
R3
5a : R3 = R4 = R5 = H
5b : R3 = F, R4 = R5 = H
5c : R3 = H, R4 = R5 =CH3
The 13C nmr spectrum of 3d showed two different
signals for gemdimethyls at ꢀ 28.0 and 29.4 respectively
indicating that they are in different planes. Lactone
carbonyl carbon appeared at ꢀ 165.5 and the carbonyl
carbon appeared at ꢀ 197.2. The other carbon signals
appeared in the usual region.
EXPERIMENTAL
General.Melting points were determined by POLMAN
melting point apparatus (Model No. MP-96) and are
uncorrected. The IR spectra (ꢁmax cm-1) were recorded on
1
Perkin-Elmer spectrophotomer. The H nmr, 13C nmr spectra
were recorded on 300 MHz Bruker-Avance instrument using

May-Jun 2007
New 3-(4-Aryl-5-oxo-5,6,7,8-tetrahydro-4H-chromen-2-yl)-2H-chromen-2-ones
709
TMS as an internal standard. The mass spectra were scanned on
Perkin-Elmer SCIEX API-2000 instrument. The purity of all
compounds was established by TLC analysis using Merck
precoated silica gel 60F254 plates (0.2 mm thickness).
CH2), 3.7 (s, 3H, OCH3), 4.39 (d, 1H, J = 6 Hz, pyran), 6.64 (d,
1H, J = 6 Hz, Pyran), 6.85 (d, 2H, J = 6 Hz, Ar-H), 7.14 (d, 2H,
J = 9Hz, Ar-H), 7.39 (d, 1H, J = 9Hz, Ar-H), 7.78 (d, 1H, J = 9
Hz, Ar-H), 8.12 (d, 1H, J = 2.1 Hz, Ar-H), 8.41 (s, 1H, C4-H of
coumarin); Anal. Calcd. for C27H23BrO5 (507.37): C, 63.91; H,
4.56. Found: C, 63.69; H, 4.60.
General Procedure for synthesis of 3-(4-aryl-5-oxo-5,6,7,8-
tetrahydro-4H-chromen-2-yl)-2H-chromen-2-ones (3a-g and
5a-c). Compound 1 or 4 (0.01 mole) was dissolved in Toluene
(30 ml) at 25°C, compound 2 (0.01 mole) and zinc bromide
(0.003 mole) were added to the solution. The resulting
suspension was heated to reflux (110 °C). The byproduct, water
was removed azeotropically using Dean stark apparatus. The
reflux was continued till the reaction gets completed (~3 hours).
Toluene was removed by distillation under reduced pressure and
recrystallised the product from isopropyl alcohol.
3-(4-(4-Fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-tetra-
hydro-4H-chromen-2-yl)-2H-chromen-2-one (3f) was
obtained by the reaction of 1b with 2b in 72% yield, mp 196-
198 °C. ir (potassium bromide): 1735 (C=O, lactone), 1666
1
(C=O), 1209 cm-1. H nmr (DMSO-d6): 1.04 (s, 3H, CH3), 1.09
(s, 3H, CH3), 2.22 (ABq, 2H, J = 15 Hz, COCH2), 2.68 (s, 2H,
CH2), 4.48 (d, 1H, J = 6 Hz, pyran), 6.64 (d, 1H, J = 3 Hz,
pyran), 7.09 – 7.68 (m, 7H, Ar-H), 7.87 (d, 1H, J = 6 Hz, Ar-H),
8.45 (s, 1H, C4-H of coumarin); Anal. Calcd. for C26H21FO4
(416.44): C, 74.98; H, 5.08. Found: C, 75.11; H, 5.10.
6-Bromo-3-(4-(4-fluorophenyl)-7,7-dimethyl-5-oxo-5,6,7,8-
tetrahydro-4H-chromen-2-yl)-2H-chromen-2-one (3g) was
obtained by the reaction of 1e with 2b in 76% yield, mp 175-177
°C; ir (potassium bromide): 1737 (C=O, lactone), 1661 (C=O),
1206 cm-1. 1H nmr (CDCl3), 1.05 (s, 3H, CH3), 1.08 (s, 3H,
CH3), 2.25 (ABq, 2H, J = 18 Hz, -COCH2), 2.56 (s, 2H, CH2),
4.53 (d, 1H, J = 6 Hz, pyran), 6.88 (d, 1H, J = 6 Hz, pyran), 7.19
– 7.29 (m, 4H, Ar-H), 7.59 – 7.68 (m, 3H, Ar-H), 8.41 (s, 1H,
C4-H of coumarin); Anal. Calcd. for C26H20BrFO4 (495.35): C,
63.04; H, 4.07. Found: C, 63.09; H, 4.07.
6-Chloro-3-(7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-
4H-chromen-2-yl)-2H-chromen-2-one (3h) was obtained by
the reaction of 1f with 2b in 70% yield, mp 190-192 °C; ir
(potassium bromide): 1736 (C=O, lactone), 1205 cm-1. 1H nmr
(CDCl3): 1.09 (s, 3H, CH3), 1.15 (s, 3H, CH3), 2.26 (ABq, 2H, -
COCH2), 2.58 (s, 2H, CH2), 4.54 (d, 1H, pyran), 6.9 (d, 1H,
pyran), 7.28 – 7.64 (m, 7H, Ar-H), 8.04 (s, 1H, Ar-H), 8.42 (s,
1H, C4-H of coumarin); Anal. Calcd. for C26H21ClO4 (432.91):
C, 72.14; H, 4.89. Found: C, 72.20; H, 4.81.
3-(5-Oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromen-2-yl)-
2H-chromen-2-one (3a) was obtained by the reaction of 1a
with 2a in 70% yield, mp 238-240 °C; ir (potassium bromide):
1
1730 (C=O, lactone), 1656 (C=O), 1208 cm-1; H nmr (DMSO-
d6): 2.05 (m, 2H, CH2), 2.34 (m, 2H, CH2), 2.78 (m, 2H, CH2),
4.47 (d, 1H, J = 6 Hz, C4-H, pyran), 6.66 (d, 1H, J = 6 Hz, C3-H,
pyran), 7.19-7.72 (m, 9H, Ar-H), 8.44 (s, 1H, C4-H of
coumarin); ms: (12.5 eV, ESI) m/z 370 (molecular ion); Anal.
Calcd. for C24H18O4 (370.4): C, 77.83; H, 4.90. Found: C,
77.78, H, 4.80.
3-(4-(4-Fluorophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromen-
2-yl)-2H-chromen-2-one (3b) was obtained by the reaction of 1b
with 2a in 74% yield, mp 231-233 °C; ir (potassium bromide) :
1717 (C=O, lactone), 1670 (C=O), 1208 cm-1; 1H nmr (DMSO-d6)
: 2.02 (m, 2H, CH2), 2.32 (m, 2H, CH2), 2.77 (m, 2H, J = 6 Hz,
CH2), 4.49 (d, 1H, J = 6 Hz, Pyran), 6.64 (d, 1H, J = 6 Hz, Pyran),
7.08 – 7.69 (m, 7H, Ar-H), 7.88 (d, 1H, Ar-H), 8.43 (s, 1H, C4-H
of coumarin); Anal. Calcd. for C24H17FO4 (388.39): C, 74.22; H,
4.41. Found: C, 74.15; H, 4.38.
3-(4-(4-Methoxyphenyl)-5-oxo-5,6,7,8-Tetrahydro-4H-chro-
men-2-yl)-2H-chromen-2-one (3c) was obtained by the reaction
of 1c with 2a in 65% yield, mp 132-134 °C; ir (potassium
bromide): 1732 (C=O, lactone), 1657 (C=O), 1280 cm-1; 1H nmr
(CDCl3) : 2.07 (m, 2H, CH2), 2.38 (m, 2H, CH2), 2.71 (m, 2H,
CH2), 3.76 (s, 3H, CH3), 4.52 (d, 1H, J = 6 Hz, pyran), 6.82 (d,
2H, J = 9 Hz, Ar-H), 6.89 (d, 1H, J = 5.14 Hz, pyran), 7.23 (d,
m, 4H, Ar-H), 7.6 – 7.66 (m, 1H, Ar-H), 7.75 (s, 1H, Ar-H),
8.47 (s, 1H, C4-H of coumarin); Anal. Calcd. for C25H20O5
(400.42): C, 74.98; H, 5.03. Found: C, 75.12; H, 4.92.
2-(5-Oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromen-2-yl)-
3H-benzo[f]chromen-3-one (5a) was obtained by the reaction of
4a with 2a in 65% yield, mp 246-248 °C; ir (potassium bromide):
1
1730 (C=O, lactone), 1656 (C=O), 1209 cm-1; H nmr (CDCl3):
2.05 (m, 2H, CH2), 2.33 (m, 2H, CH2), 2.90 (m, 2H, -COCH2),
4.50 (d, 1H, J = 6 Hz, Pyran), 6.72 (d, 1H, J = 6 Hz, pyran), 7.16-
7.29 (m, 5H, Ar-H), 7.59 – 7.83 (m, 3H, Ar-H), 8.09 (d, 1H,J = 9
Hz, Ar-H), 8.23 (d, 1H, J = 9 Hz, Ar-H), 8.66 (d, 1H, J = 8.7 Hz,
Ar-H), 9.07 (s, 1H, C4-H of coumarin); Anal. Calcd. for C28H20O4
(420.46): C, 79.98; H, 4.79. Found: C, 79.92; H, 4.70.
3-(7,7-Dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-2-yl)-2H-chromen-2-one (3d) was obtained by the
reaction of 1a with 2b in 75% yield, mp 140-142 °C; ir
(potassium bromide): 1738.8 (C=O, lactone), 1656 (C=O), 1207
2-(4-(4-Fluorophenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromen-
2-yl)-3H-benzo[f]chromen-3-one (5b) was obtained by the
reaction of 4b with 2a in 73% yield, mp 238-240 °C; ir
(potassium bromide): 1730 (C=O, lactone), 1655 (C=O), 1217
1
cm-1; H nmr (DMSO-d6): 1.05 (s, 3H, CH3), 1.10 (s, 3H, CH3),
2.16 (ABq, 2H, -COCH2), 2.69 (s, 2H, CH2), 4.45 (d, 1H, J = 6
Hz, pyran), 6.66 (d, 1H, J = 6 Hz, pyran), 7.18 – 7.85 (m, 9H,
Ar-H), 8.44 (s, 1H, C4-H of coumarin); 13C nmr (DMSO-d6)
28.0, 29.4, 32.7, 34.8, 41.2, 51.0, 111.9, 115.8, 116.1, 116.7,
118.7, 119.5, 125.7, 130.0, 130.3, 130.4, 133.4, 139.4, 141.4,
141.9, 153.4, 158.3, 160.1, 163.3, 165.5, 197.2; ms: m/z 398
(molecular ion); Anal. Calcd. for C26H22O4 (398.45): C, 78.37;
H, 5.56. Found: C, 78.28; H, 5.46.
1
cm-1; H nmr (CDCl3) : 2.12 (m, 2H, CH2), 2.44 (m, 2H, CH2),
2.84 (m, 2H, CH2), 4.62 (d, 1H, J = 6 Hz, pyran), 6.94 (d, 1H, J
= 6 Hz, pyran), 7.30 (m, 2H, Ar-H), 7.50-7.98 (m, 6H, Ar-H),
8.05 (d, 1H, Ar-H), 8.37 (d, 1H, Ar-H), 8.93 (s, 1H, C4-H of
coumarin); Anal. Calcd. for C28H19FO4 (438.45): C, 76.70; H,
4.36. Found: C, 76.40, H, 4.27.
2-(7,7-Dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-2-yl)-3H-benzo[f]chromen-3-one (5c) was obtained
by the reaction of 4a with 2b in 78% yield, mp 208-210°C; ir
(potassium bromide): 1721 (C=O, lactone), 1655 (C=O), 1213
cm-1. 1H nmr (CDCl3) : 1.13 (s, 3H, CH3), 1.19 (s, 3H, CH3),
2.27 (ABq, 2H, -COCH2), 2.56 (s, 2H, CH2), 4.59 (d, 1H, J = 5.4
Hz, pyran), 6.96 (d, 1H, J = 5.4 Hz, pyran), 7.26 – 7.75 (m, 7H,
6-Bromo-3-(4-(4-methoxyphenyl)-7,7-dimethyl-5-oxo-5,6,7,
8-tetrahydro-4H-chromen-2-yl)-2H-chromen-2-one (3e) was
obtained by the reaction of 1d with 2b in 72% yield, mp 178-
180 °C; ir (potassium bromide) : 1741 (C=O, lactone), 1656
1
(C=O), 1205 cm-1; H nmr (DMSO-d6): 1.04 (s, 3H, CH2), 1.09
(s, 3H, CH3), 2.29 (ABq, 2H, J = 18 Hz, -COCH2), 2.58 (s, 2H,

710
V. R. Rao and V. R. Reddy
Vol 44
[4] Y. Morianka and K. Takahashi, Japan Kokai, 7717, 498 (to
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(1977).
Ar-H), 7.93 – 8.02 (m, 3H, Ar-H), 8.35 (d, 1H, Ar-H), 8.9 (s,
1H, C4-H of coumarin); Anal. Calcd. for C30H24O4 (448.51): C,
80.33; H, 5.39. Found: C, 80.26, H, 5.30.
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